Antibodies to block Omicron identified, third dose really useful

Antibodies to block Omicron identified, third dose 'really useful'

The Omicron variant has 37 mutations in the nail protein. (representative)


During a recent study, an international team of researchers identified antibodies that neutralize Omicron and other SARS-CoV-2 variants.

These antibodies target regions of the virus tip protein that remain substantially unchanged when the viruses mutate. The results of the study were published in the journal Nature.

By identifying the targets for these “broadly neutralizing” antibodies on the nail protein, it may be possible to design vaccines and antibody treatments that will be effective against not only the Omicron variant, but other variants that may emerge in the future, said David Veesler, an investigator at the Howard Hughes Medical Institute and associate professor of biochemistry at the University of Washington School of Medicine in Seattle.

“This finding tells us that by focusing on antibodies that target these highly conserved sites on the nail protein, there is a way to overcome the continuous development of the virus,” Veesler said.

Veesler led the research project together with Davide Corti from Humabs Biomed SA, Vir Biotechnology, in Switzerland. The lead authors of the study were Elisabetta Cameroni and Christian Saliba (Humabs), John E. Bowen (UW Biochemistry) and Laura Rosen (Vir).

The omicron variant has 37 mutations in the spike protein, which it uses to lock in and invade cells. This is an unusually high number of mutations. It is believed that these changes partly explain why the variant has been able to spread so rapidly, to infect people who have been vaccinated, and to re-infect those who have been infected in the past.

“The main questions we tried to answer were: how has this constellation of mutations in the tip protein of the omicron variant affected its ability to bind to cells and avoid the antibody responses of the immune system,” Veesler said.

[Veesler and his colleagues speculate that omicron’s large number of mutations might have accumulated during a prolonged infection in someone with a weakened immune system or by the virus jumping from humans to an animal species and back again.]

To assess the effect of these mutations, the researchers constructed a deactivated, non-replicating virus, called a pseudovirus, to produce surface surface proteins, as coronavirus does. They then created pseudoviruses that had peak proteins with the omicron mutations and those found on the earliest variants identified in the pandemic.

The researchers first examined how well the different versions of the nail protein were able to bind to a protein on the surface of cells that the virus uses to lock in and enter the cell. This protein is called the angiotensin-converting enzyme-2 (ACE2) receptor.

They found that the Omicron variant nail protein was able to bind 2.4 times better than the nail protein found in the virus, which was isolated at the very beginning of the pandemic.

“It’s not a huge increase,” Veesler noted, “but in the SARS outbreak of 2002-2003, mutations in the nail protein that increased affinity were associated with higher transferability and infectivity.”

They also found that the Omicron variant was able to bind to mouse ACE2 receptors effectively, suggesting that Omicron may be able to “ping-pong” between humans and other mammals.

The researchers looked at how well antibodies to previous isolates of the virus protected against the Omicron variant. They did so by using antibodies from patients who had previously been infected with previous versions of the virus, vaccinated against previous virus strains, or had become infected and then vaccinated.

They found that antibodies from humans who had been infected with previous strains and from those who had received one of the six most widely used vaccines currently available all had reduced ability to block infection.

Antibodies from previously infected individuals and those who had received the Sputnik V or Sinopharm vaccines, as well as a single dose of Johnson & Johnson, had little or no ability to block – or “neutralize” – the entry of the omicron variant into cells. Antibodies from individuals who had received two doses of the Moderna, Pfizer / BioNTech, and AstraZeneca vaccines retained some neutralizing activity, albeit reduced by 20 to 40-fold, much more than any other variant.

Antibodies from people who had been infected recovered and then given two doses of the vaccine had also decreased activity, but the reduction was smaller, about five times, clearly showing that vaccination after infection is useful.

Antibodies from humans, in this case a group of renal dialysis patients who had received a booster with a third dose of the mRNA vaccines produced by Moderna and Pfizer / BioNTech, showed only a 4-fold reduction in neutralizing activity. “This shows that a third dose is really, really useful against omicron,” Veesler said.

All but one antibody treatment currently approved or approved for use with patients exposed to the virus had no or markedly reduced activity against omicron in the laboratory. The exception was an antibody called sotrovimab, which had a two to three-fold reduction in neutralizing activity, the study shows.

However, when testing a larger panel of antibodies that have been generated against earlier versions of the virus, the researchers identified four classes of antibodies that retained their ability to neutralize the omicron. Members of each of these classes target one of four specific regions of the peak protein present in not only SARS-CoV-2 variants, but also a group of related coronaviruses, called sarbecoviruses. These sites on the protein may continue because they play a significant function that the protein would lose if they mutated. Such areas are called “preserved”.

The discovery that antibodies are able to neutralize through the recognition of conserved regions in so many different variants of the virus suggests that the design of vaccines and antibody treatments targeting these regions could be effective against a wide range of variants. , which occurs through mutation, Veesler said.

(With the exception of the headline, this story has not been edited by NDTV staff and is published from a syndicated feed.)


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